Association between GABRA1 and drinking behaviors in the Collaborative Study on the Genetics of Alcoholism sample

Danielle M. Dick, Jevon Plunkett, Leah Flury Wetherill, Xiaoling Xuei, Alison Goate, Victor Hesselbrock, Marc Schuckit, Raymond Crowe, Howard Edenberg, Tatiana Foroud

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Background: A wealth of literature supports the role of γ-aminobutyric acid (GABA) in neurobiological pathways contributing to alcohol dependence and related phenotypes. Animal studies have consistently tied rodent homologs of the GABAA receptor genes on human chromosome 5q to alcohol-related behaviors; however, human studies have produced mixed results. Family-based association analyses previously conducted in the Collaborative Study on the Genetics of Alcoholism (COGA) sample yielded no evidence of association with Diagnostic and Statistical Manual of Mental Disorder - fourth edition (DSM-IV) alcohol dependence and these genes. As a follow-up to that study, we examined several alcohol-related behaviors in the COGA sample as follows: (1) a broader definition of alcohol dependence, including DSM-III-R symptoms and Feighner criteria (referred to as COGA alcohol dependence); (2) withdrawal; (3) history of alcohol-induced blackouts; (4) level of response to alcohol; (5) age of onset of regular drinking; and (6) age at first drunkenness. Methods: Family-based association tests were conducted, using multiple single-nucleotide polymorphisms (SNPs) in each of the 4 GABAA receptor genes on chromosome 5q. Results: In GABRA1, we found evidence of association with several of the drinking behavior phenotypes, including COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. We did not find consistent evidence of association with the remaining genes and any of the phenotypes. Conclusions: We found evidence for association between GABRA1 and COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. These analyses suggest that efforts to characterize genetic contributions to alcohol dependence may benefit by examining alcohol-related behaviors in addition to clinical alcohol dependence diagnoses.

Original languageEnglish
Pages (from-to)1101-1110
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number7
DOIs
StatePublished - Jul 2006

Fingerprint

Drinking Behavior
Alcoholism
Alcohols
Alcoholic Intoxication
Diagnostic and Statistical Manual of Mental Disorders
Genes
GABA-A Receptors
Phenotype
Genetics
Chromosomes
Aminobutyrates
Human Chromosomes
Age of Onset
gamma-Aminobutyric Acid
Drinking
Single Nucleotide Polymorphism
Polymorphism
Rodentia

Keywords

  • Alcohol Dependence
  • Association Analyses
  • Chromosome 5
  • Drinking Behavior
  • GABA Receptor Genes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Association between GABRA1 and drinking behaviors in the Collaborative Study on the Genetics of Alcoholism sample. / Dick, Danielle M.; Plunkett, Jevon; Wetherill, Leah Flury; Xuei, Xiaoling; Goate, Alison; Hesselbrock, Victor; Schuckit, Marc; Crowe, Raymond; Edenberg, Howard; Foroud, Tatiana.

In: Alcoholism: Clinical and Experimental Research, Vol. 30, No. 7, 07.2006, p. 1101-1110.

Research output: Contribution to journalArticle

Dick, Danielle M. ; Plunkett, Jevon ; Wetherill, Leah Flury ; Xuei, Xiaoling ; Goate, Alison ; Hesselbrock, Victor ; Schuckit, Marc ; Crowe, Raymond ; Edenberg, Howard ; Foroud, Tatiana. / Association between GABRA1 and drinking behaviors in the Collaborative Study on the Genetics of Alcoholism sample. In: Alcoholism: Clinical and Experimental Research. 2006 ; Vol. 30, No. 7. pp. 1101-1110.
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T1 - Association between GABRA1 and drinking behaviors in the Collaborative Study on the Genetics of Alcoholism sample

AU - Dick, Danielle M.

AU - Plunkett, Jevon

AU - Wetherill, Leah Flury

AU - Xuei, Xiaoling

AU - Goate, Alison

AU - Hesselbrock, Victor

AU - Schuckit, Marc

AU - Crowe, Raymond

AU - Edenberg, Howard

AU - Foroud, Tatiana

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AB - Background: A wealth of literature supports the role of γ-aminobutyric acid (GABA) in neurobiological pathways contributing to alcohol dependence and related phenotypes. Animal studies have consistently tied rodent homologs of the GABAA receptor genes on human chromosome 5q to alcohol-related behaviors; however, human studies have produced mixed results. Family-based association analyses previously conducted in the Collaborative Study on the Genetics of Alcoholism (COGA) sample yielded no evidence of association with Diagnostic and Statistical Manual of Mental Disorder - fourth edition (DSM-IV) alcohol dependence and these genes. As a follow-up to that study, we examined several alcohol-related behaviors in the COGA sample as follows: (1) a broader definition of alcohol dependence, including DSM-III-R symptoms and Feighner criteria (referred to as COGA alcohol dependence); (2) withdrawal; (3) history of alcohol-induced blackouts; (4) level of response to alcohol; (5) age of onset of regular drinking; and (6) age at first drunkenness. Methods: Family-based association tests were conducted, using multiple single-nucleotide polymorphisms (SNPs) in each of the 4 GABAA receptor genes on chromosome 5q. Results: In GABRA1, we found evidence of association with several of the drinking behavior phenotypes, including COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. We did not find consistent evidence of association with the remaining genes and any of the phenotypes. Conclusions: We found evidence for association between GABRA1 and COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. These analyses suggest that efforts to characterize genetic contributions to alcohol dependence may benefit by examining alcohol-related behaviors in addition to clinical alcohol dependence diagnoses.

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KW - Drinking Behavior

KW - GABA Receptor Genes

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